Is F7 p.Arg430His (c.1289G>A) pathogenic?

F7 p.Arg430His (c.1289G>A) is classified Likely benign in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.0593); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with F7 p.Arg430His (c.1289G>A)?

F7 p.Arg430His (c.1289G>A) is associated with Inborn genetic diseases (ClinVar).

How common is F7 p.Arg430His (c.1289G>A) in the general population?

F7 p.Arg430His (c.1289G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about F7 p.Arg430His (c.1289G>A)?

AlphaMissense predicts likely benign (score 0.0593) — an in-silico prediction, not a clinical call.

F7 p.Arg430His

c.1289G>A · rs369006583 · VCV3091482

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0593 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0593	likely benign
REVEL	0.237	benign-leaning
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.5
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	0.109	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R452H vs ClinVar R430H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00206% 33/1,605,272 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
African / African-American	0.004%	24,977
Remaining individualsnot grpmax-eligible	0.0032%	31,211
European (non-Finnish)	0.00212%	47,199
Admixed American	0.00167%	59,990

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: F7
Protein: p.Arg430His
Coding: c.1289G>A
MANE Select: NM_019616
dbSNP: rs369006583
Type: single nucleotide variant
Location: chr13:113118962 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB
Residue 430: the peptidase s1 domain

Full F7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F7 p.Arg434His Uncertain significance ★★ ⚠ same condition
F7 p.Asp234Asn Uncertain significance ★★ ⚠ same condition
F7 p.Cys232Ser Uncertain significance ★★ ⚠ same condition
F7 p.Glu27Lys Uncertain significance ★★ ⚠ same condition
F7 p.His30Tyr Uncertain significance ★★ ⚠ same condition
F7 p.Lys147Arg Uncertain significance ★★ ⚠ same condition
F7 p.Thr345Ser Uncertain significance ★★ ⚠ same condition
F7 p.Trp225Cys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/f7-p-arg430his (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown